Natural Treatments for the Management of Emotional Dysregulation in Youth With Non-verbal Learning Disability (NVLD) and/or Autism Spectrum Disorders (ASD)

• Open-label Treatment with Omega-3 Fatty Acids + Inositol (Drug): Open-label Treatment with Omega-3 Fatty Acids + Inositol
• Open-label Treatment with N-acetylcysteine (Drug): Open-label Treatment with acetylcysteine

Primary outcomes

• Mean Change in the Parent-Young Mania Rating Scale (P-YMRS) Score [Baseline to 6 Weeks]: The YMRS consists of 11 items rated on a scale from 0 (symptoms not present) to 4 (symptoms extremely severe). It is used to assess manic symptoms. The YMRS score ranges from 0-60. Questions are asked about the last week. This scale is generally accepted as the main outcome measure in studies of pediatric bipolar disorder and is linked directly to the core symptoms of mania. Higher scores indicate more severe manic symptoms.

Secondary outcomes

• Mean Change in the Parent-completed Children's Depression Inventory (CDI) [Baseline to 6 Weeks]: The CDI consists of 27 items quantifying symptoms such as depressed mood, hedonic capacity, vegetative functions, self-evaluation, and interpersonal behaviors. Each item consists of three statements graded in order of increasing severity from 0 to 2; parents select the one that characterized their child's symptoms best during the past 1 week. The item scores are combined into a total depression score, which ranges from 0 to 54. A higher CDI score means a higher depressive state.
• Mean Change in the NIMH Clinical Global Improvement Scale (CGI) [Baseline to 6 Weeks]: The CGI-BPD-S is a clinician-rated measure of bipolar disorder severity. Severity scores range from 1 (normal, not at all ill) to 7 (among the most extremely ill patients). The outcome reported reflects the change from baseline in CGI-BPD-S scores and negative scores represent improvement (i.e., decrease in severity from baseline).

Sex: All, ages: 5 Years to 17 Years

Inclusion Criteria:

* A previous established diagnosis of non-verbal learning disability (NVLD) or DSM-V Autism Spectrum Disorder and/ or combined T-scores on the Child Behavior Checklist > 195 on the Withdrawn + Social Problems + Thought Problems subscales.
* Current symptoms of emotional dysregulation as indicated by combined T-scores on the Child Behavior Checklist > 180 on the Anxiety/Depression + Aggression + Attention subscales.
* Subjects and their caregivers must be English-speaking and have a level of understanding sufficient to communicate intelligently with the investigator and study coordinator, and to cooperate with all tests and examinations required by the protocol.
* Subjects and their caregivers must be willing and able to comply with all study procedures.
* Each subject and his/her authorized legal representative must understand the nature of the study. The subject's authorized legal representative must sign an informed consent document and the subject must sign an informed assent document.
* Subject must be able to swallow pills.
* Subject must have access to a computer with a camera, speaker, microphone, and internet connection.

Exclusion Criteria:

* Investigator and his/her immediate family; defined as the investigator's spouse, parent, child, grandparent, or grandchild.
* Serious or unstable illness including hepatic, renal, gastroenterological, respiratory, cardiovascular (including ischemic heart disease), endocrinologic, neurologic, immunologic, or hematologic disease.
* History of bleeding diathesis, including those with von Willebrand disease.
* Uncorrected hypothyroidism or hyperthyroidism.
* History of sensitivity to omega-3 fatty acids, inositol or NAC. A non-responder or history of intolerance to omega-3 fatty acid, inositol or NAC after 2 months of treatment at adequate doses as determined by the clinician.
* Severe allergies or multiple adverse drug reactions.
* Unstable or untreated seizure disorder.
* DSM-IV substance use, abuse or dependence.
* Judged clinically to be at serious suicidal risk for C-SSRS score ≥ 4.
* Current diagnosis of schizophrenia.
* Current diagnosis or symptoms of psychosis.
* IQ < 70.
* Pregnant or nursing.
* Weighs less than 12.5kg.

Participant flow

Outcome results

• Mean Change in the Parent-Young Mania Rating Scale (P-YMRS) Score (Primary), Mean, Units on a Scale: Omega-3 Fatty Acid Plus Inositol 0.0 +/- 7.9; N-Acetylcysteine -2.6 +/- 8.1
• Mean Change in the Parent-completed Children's Depression Inventory (CDI) (Secondary), Mean, Units on a Scale: Omega-3 Fatty Acids + Inositol -3.4 +/- 7.7; N-acetylcysteine -1.3 +/- 6.5
• Mean Change in the NIMH Clinical Global Improvement Scale (CGI) (Secondary), Mean, Units on a Scale: Omega-3 Fatty Acids + Inositol -1.1 +/- 1.3; N-acetylcysteine -0.7 +/- 1.1

Adverse events

Time frame: Adverse events were monitored from enrollment until end of study, on average 6 weeks.

Serious adverse events by term

Other adverse events by term

• Study Protocol (PDF, 2023-02-22)
• Statistical Analysis Plan (PDF, 2025-04-23)

• Janet Wozniak, MD, Principal investigator, Massachusetts General Hospital